Recent studies from our laboratory indicate that the close functional relationship between hematopoiesis and the vascular system first identified in early embryonic development extends into adult life. A single adult hematopoietic stem cell can differentiate into endothelial cells and blood cells, demonstrating the existence of adult cells with hemangioblast activity. Although bone marrow- derived hematopoietic stem cells (HSCs) and their progeny are thought to contribute to angiogenesis, relatively little is known about the identity of the progenitor cells involved and the mechanisms by which they contribute to blood vessel repair. We now hypothesize that the differentiation of HSCs into mature endothelial cells and the production of pro-angiogenic cytokines by HSCs and/or their progeny are critical factors regulating vascular endothelial homeostasis. To test this hypothesis, we propose to 1) determine the contribution of hematopoietic progenitors to the endothelial cell compartment during normal development;2) evaluate the phenotype and functional activity of circulating pro-angiogenic hematopoietic cells;3) determine the functional role of bone marrow derived endothelial cell progenitors during tissue regeneration. This research is significant as it is designed to identify novel cellular mechanisms responsible for vascular and hematopoietic system regeneration. PUBLIC HEALTH RELEVANCE The purpose of these studies is to enhance our knowledge of the close functional relationship between blood cell development and the vascular system. The results of this research have important implications for our understanding of disorders of the bone marrow and the vascular system. Ultimately this will lead to the identification of potential therapeutic targets for a number of diseases including leukemia, coronary artery disease and peripheral vascular disease.